ArticleProceedings of the National Academy of Sciences of the United States of America2016
Activation of integrin α5 mediated by flow requires its translocation to membrane lipid rafts in vascular endothelial cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 114 citations in OpenAlex.
- Human Cell-Derived Extracellular Matrix Modulates Endothelial Cell Morphology and Metabolism in Response to Fluid Shear Stress.ACS biomaterials science & engineering · 2026Article
- Oscillatory shear stress-driven endothelial-to-mesenchymal transition: a critical mechanical signal transduction mechanism in atherosclerosis progression.Cell death discovery · 2026Review
- Critical Role of the Endothelial αV/β5 Integrin Receptor Signaling Pathway in Promoting Irisin-induced Hippocampal BDNF Expression.Molecular neurobiology · 2025Article
- Age-Related Dysregulation of α5β1 and αvβ3 Integrin Activity Alters Contractile Properties of Trabecular Meshwork Cells.Investigative ophthalmology & visual science · 2025Article
- Integrin-Specific Signaling Drives ER Stress-Dependent Atherogenic Endothelial Activation.bioRxiv : the preprint server for biology · 2025Article
- Environmental Toxicants and Their Disruption of Integrin Signaling in Lipid Rafts.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Review
- Metaboloepigenetics: Role in the Regulation of Flow-Mediated Endothelial (Dys)Function and Atherosclerosis.Cells · 2025Review
- Phosphorylation of endothelial histone H3.3 serine 31 by PKN1 links flow-induced signaling to proatherogenic gene expression.Nature cardiovascular research · 2025Article
- Regulatory role of cholesterol in modulating actin dynamics and cell adhesive interactions in the trabecular meshwork.bioRxiv : the preprint server for biology · 2024Article
- Mechanosensory entities and functionality of endothelial cells.Frontiers in cell and developmental biology · 2024Review
- Convergence of Calcium Channel Regulation and Mechanotransduction in Skeletal Regenerative Biomaterial Design.Advanced healthcare materials · 2023Review
- Mutant p53-ENTPD5 control of the calnexin/calreticulin cycle: a druggable target for inhibiting integrin-α5-driven metastasis.Journal of experimental & clinical cancer research : CR · 2023Article
- Endothelial mechanobiology in atherosclerosis.Cardiovascular research · 2023Review
- Vascular mechanotransduction.Physiological reviews · 2023Review
- A transcriptomic pan-cancer signature for survival prognostication and prediction of immunotherapy response based on endothelial senescence.Journal of biomedical science · 2023Article
- Integrin-Dependent Cell-Matrix Adhesion in Endothelial Health and Disease.Circulation research · 2023Review
- Atherosclerosis and endothelial mechanotransduction: current knowledge and models for future research.American journal of physiology. Cell physiology · 2023Review
- Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023Review
- Role of integrins in the development of fibrosis in the trabecular meshwork.Frontiers in ophthalmology · 2023Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Local flow patterns determine the uneven distribution of atherosclerotic lesions. Membrane lipid rafts and integrins are crucial for shear stress-regulated endothelial function. In this study, we investigate the role of lipid rafts and integrin α5 in regulating the inflammatory response in endothelial cells (ECs) under atheroprone versus atheroprotective flow. Lipid raft proteins were isolated from ECs exposed to oscillatory shear stress (OS) or pulsatile shear stress, and then analyzed by quantitative proteomics. Among 396 proteins redistributed in lipid rafts, integrin α5 was the most significantly elevated in lipid rafts under OS. In addition, OS increased the level of activated integrin α5 in lipid rafts through the regulation of membrane cholesterol and fluidity. Disruption of F-actin-based cytoskeleton and knockdown of caveolin-1 prevented the OS-induced integrin α5 translocation and activation. In vivo, integrin α5 activation and EC dysfunction were observed in the atheroprone areas of low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice, and knockdown of integrin α5 markedly attenuated EC dysfunction in partially ligated carotid arteries. Consistent with these findings, mice with haploinsufficency of integrin α5 exhibited a reduction of atherosclerotic lesions in the regions under atheroprone flow. The present study has revealed an integrin- and membrane lipid raft-dependent mechanotransduction mechanism by which atheroprone flow causes endothelial dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.